Scholarlink

<p>RNA-binding proteins play a key role in post-transcriptional events, such as mRNA splicing, transport, stability, translation and decay. Dysregulation of RNA life can have dramatic consequences. CELF RNA-binding proteins appear to be essential during embryo development. In this study, we identified 15 patients with heterozygous missense or loss-of-function variants in the <i>CELF4</i> gene by exome or genome sequencing. All variants affecting the N-terminus of the protein are essential and sufficient for the RNA-binding and splicing activity or RRM domains. Most patients presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14) that began in childhood. Clinical features are similar to the reported celf4-mouse mutant phenotype. This study highlights the essential role of <i>CELF4</i> in development and its involvement as a novel etiology of neurodevelopmental disorders with obesity.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Heterozygous CELF4 variants in the N-term region crucial for the RNA-binding activity lead to neurodevelopmental disorder and obesity

  • 期刊论文

  • 发表日期：

    2025年3月19日

查看全文
  • Ange-Line Bruel,
  • Anneke T. Vulto-vanSilfhout,
  • Frédéric Bilan,
  • Gwenaël Le Guyader,
  • Brigitte Gilbert-Dussardier,
  • Xavier Le Guillou,
  • Sophie Rondeau,
  • Marlène Rio,
  • Kristen N. Lee,
  • Adelyn Beil,
  • Mohnish Suri,
  • François Guerin,
  • Valentin Ruault,
  • Alice Goldenberg,
  • François Lecoquierre,
  • Nicole Bertsch,
  • Rhonda Anderson,
  • Xiao-Ru Yang,
  • Micheil Inness,
  • Emi Rikeros-Orozco,
  • Maria Palomares-Bralo,
  • Jennifer Cassady Hayek,
  • Jennifer Cech,
  • Ankita Jhuraney,
  • Runjun D. Kumar,
  • Saadet Mercimek-Andrews,
  • Anastasia Ambrose,
  • Erin N. Wakeling,
  • Ingrid M. Wentzensen,
  • Erin Torti,
  • Catherine Gooch,
  • Laurence Faivre,
  • Christophe Philippe,
  • Yannis Duffourd,
  • Antonio Vitobello,
  • Christel Thauvin-Robinet

摘要

RNA-binding proteins play a key role in post-transcriptional events, such as mRNA splicing, transport, stability, translation and decay. Dysregulation of RNA life can have dramatic consequences. CELF RNA-binding proteins appear to be essential during embryo development. In this study, we identified 15 patients with heterozygous missense or loss-of-function variants in the CELF4 gene by exome or genome sequencing. All variants affecting the N-terminus of the protein are essential and sufficient for the RNA-binding and splicing activity or RRM domains. Most patients presented with neurodevelopmental disorders including global developmental delay/intellectual disability (11/14), seizures (9/15) and overweight/obesity (10/14) that began in childhood. Clinical features are similar to the reported celf4-mouse mutant phenotype. This study highlights the essential role of CELF4 in development and its involvement as a novel etiology of neurodevelopmental disorders with obesity.